tbuckley/cabot-search huggingface dataset:
Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study
Authors: Manuel Weber, David Kersting, Burkhard Riemann, Tim Brandenburg, Dagmar Führer-Sakel, Frank Grünwald, Michael C. Kreissl, Henning Dralle, Frank Weber, Kurt Werner Schmid, Ken Herrmann, Walter Jentzen, Hong Grafe, Christoph Rischpler, Sarah Theurer, Andreas Bockisch, James Nagarajah, Wolfgang P. Fendler
Journal: Clinical Cancer Research (2022)

Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC.In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic.Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0-421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) < 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each.Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success. See related commentary by Cabanillas et al., p. 4164.
Hippo Signaling in the Ovary: Emerging Roles in Development, Fertility, and Disease
Authors: Kendra L Clark, Jitu W George, Emilia Przygrodzka, Michele R Plewes, Guohua Hua, Cheng Wang, John S Davis
Journal: Endocrine Reviews (2022)

Abstract Emerging studies indicate that the Hippo pathway, a highly conserved pathway that regulates organ size control, plays an important role in governing ovarian physiology, fertility, and pathology. Specific to the ovary, the spatiotemporal expression of the major components of the Hippo signaling cascade are observed throughout the reproductive lifespan. Observations from multiple species begin to elucidate the functional diversity and molecular mechanisms of Hippo signaling in the ovary in addition to the identification of interactions with other signaling pathways and responses to various external stimuli. Hippo pathway components play important roles in follicle growth and activation, as well as steroidogenesis, by regulating several key biological processes through mechanisms of cell proliferation, migration, differentiation, and cell fate determination. Given the importance of these processes, dysregulation of the Hippo pathway contributes to loss of follicular homeostasis and reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency, and ovarian cancers. This review highlights what is currently known about the Hippo pathway core components in ovarian physiology, including ovarian development, follicle development, and oocyte maturation, while identifying areas for future research to better understand Hippo signaling as a multifunctional pathway in reproductive health and biology.
Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice
Authors: Mingyue Li, Weina Guo, Yalan Dong, Wenzhu Wang, Chunxia Tian, Zili Zhang, Ting Yu, Haifeng Zhou, Yang Gui, Kaming Xue, Junyi Li, Feng Jiang, Alexey Sarapultsev, Huafang Wang, Ge Zhang, Shanshan Luo, Heng Fan, Desheng Hu
Journal: Genomics Proteomics & Bioinformatics (2022)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.
Association Between Exposure to Outdoor Artificial Light at Night and Sleep Disorders Among Children in China
Authors: Le-Bing Wang, Yan-Chen Gong, Qiu-Ling Fang, Xin-Xin Cui, Shyamali C. Dharmage, Bin Jalaludin, Luke D. Knibbs, Michael S. Bloom, Yuming Guo, Li-Zi Lin, Xiao-Wen Zeng, Bo-Yi Yang, Gongbo Chen, Ru-Qing Liu, Yunjiang Yu, Li-Wen Hu, Guang-Hui Dong
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Healthy sleep has an important role in the physical and mental health of children. However, few studies have investigated the association between outdoor artificial light at night (ALAN) and sleep disorders in children. <h3>Objective</h3> To explore the associations between outdoor ALAN exposure and sleep disorders in children. <h3>Design, Setting, and Participants</h3> This population-based cross-sectional study, part of the National Chinese Children Health Study, was conducted from April 1, 2012, to June 30, 2013, in the first stage and from May 1, 2016, to May 31, 2018, in the second stage in 55 districts of 14 cities in China. This analysis included 201 994 children and adolescents aged 2 to 18 years. Data were analyzed from February 20 to March 21, 2022. <h3>Exposures</h3> Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's residential address obtained from the satellite imagery data, with a resolution of approximately 500 m. <h3>Main Outcomes and Measures</h3> Sleep disorders were measured by the Chinese version of the Sleep Disturbance Scale for Children. Generalized linear mixed models were used to estimate the associations of outdoor ALAN with sleep scores and sleep disorders. <h3>Results</h3> The study included 201 994 children and adolescents (mean [SD] age, 11.3 [3.2] years; 106 378 boys [52.7%]), 7166 (3.5%) of whom had sleep disorder symptoms. Outdoor ALAN exposure of study participants ranged from 0.02 to 113.48 nW/cm<sup>2</sup>/sr. Compared with the lowest quintile (Q1) of outdoor ALAN exposure, higher quintiles of exposure (Q2-Q5) were associated with an increase in total sleep scores of 0.81 (95% CI, 0.66-0.96) in Q2, 0.83 (95% CI, 0.68-0.97) in Q3, 0.62 (95% CI, 0.46-0.77) in Q4, and 0.53 (95% CI, 0.36-0.70) in Q5. Higher quintiles of exposure were also associated with odds ratios for sleep disorder of 1.34 (95% CI, 1.23-1.45) in Q2, 1.43 (95% CI, 1.32-1.55) in Q3, 1.31 (95% CI, 1.21-1.43) in Q4, and 1.25 (95% CI, 1.14-1.38) in Q5. Similar associations were observed for sleep disorder subtypes. In addition, greater effect estimates were found among children younger than 12 years. <h3>Conclusions and Relevance</h3> The findings of this cross-sectional study suggest that sleep disorders are more prevalent among children residing in areas with high levels of outdoor ALAN and the associations are generally stronger in children younger than 12 years. These findings further suggest that effective control of outdoor ALAN may be an important measure for improving the quality of children's sleep.
Eliminating METTL1‐mediated accumulation of PMN‐MDSCs prevents hepatocellular carcinoma recurrence after radiofrequency ablation
Authors: Xuezhen Zeng, Guanrui Liao, Shumin Li, Haining Liu, Xiao Zhao, Shuang Li, Kai Lei, Shenghua Zhu, Zhihang Chen, Yi Zhao, Xuxin Ren, Tianhong Su, Alfred Sze‐Lok Cheng, Sui Peng, Shuibin Lin, Ji Wang, Shuling Chen, Ming Kuang
Journal: Hepatology (2022)

Radiofrequency ablation (RFA) is an important curative therapy in hepatocellular carcinoma (HCC), but recurrence rate remains as high as all the other HCC therapeutic modalities. Methyltransferase 1 (METTL1), an enzyme for m 7 G tRNA modification, was reported to promote HCC development. Here, we assessed the role of METTL1 in shaping the immunosuppressive tumor microenvironment after insufficient RFA (iRFA).By immunohistochemistry and multiplex immunofluorescence (mIF) staining, we showed that METTL1 expression was enhanced in post-RFA recurrent HCC, accompanied by increased CD11b + CD15 + polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) and decreased CD8 + T cells. Mechanistically, heat-mediated METTL1 upregulation enhanced TGF-β2 translation to form the immunosuppressive environment by induction of myeloid-derived suppressor cell. Liver-specific overexpression or knockdown of Mettl1 significantly affected the accumulation of PMN-MDSCs and subsequently affected CD8 + T cell infiltration. Complete RFA successfully eliminated the tumor, whereas iRFA-treated mice exhibited enhanced tumor growth and metastasis with increased PMN-MDSC accumulation and decreased CD8 + T cells compared to sham surgery. Interrupting METTL1-TGF-β2-PMN-MDSC axis by anti-Ly6G antibody, or knockdown of hepatoma-intrinsic Mettl1 or Tgfb2 , or TGF-β signaling blockade significantly mitigated tumor progression induced by iRFA and restored CD8 + T cell population.Our study sheds light on the pivotal role of METTL1 in modulating an immunosuppressive microenvironment and demonstrated that interrupting METTL1-TGF-β2-PMN-MDSC axis could be a therapeutic strategy to restore antitumor immunity and prevent HCC recurrence after RFA treatment, meriting further clinical studies.
Cancer risk in adherent users of polyurethane foam-containing CPAP devices for sleep apnoea
Authors: Grégoire Justeau, Chloé Gervès-Pinquié, Marie Jouvenot, Thierry Pigeanne, Sandrine Launois, Laurene Leclair-Visonneau, Philippe Masson, Acya Bizieux-Thaminy, Sébastien Bailly, Nicole Meslier, Abdelkebir Sabil, Jean-Louis Racineux, Wojciech Trzepizur, Frédéric Gagnadoux
Journal: European Respiratory Journal (2022)

<b>Sustained and adherent CPAP therapy of obstructive sleep apnoea using Philips Respironics devices containing polyester-based polyurethane foam, was not associated with an increased risk of cancer after a median follow-up time of 7.2 years</b>https://bit.ly/3vBpUQE
Response to Open Peer Commentaries: On Social Harms, Big Tech, and Institutional Accountability
Authors: James A. Anderson, Melissa D. McCradden, Elizabeth A. Stephenson
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:Bridging the AI Chasm: Can EBM Address Representation and Fairness in Clinical Machine Learning?Broadening the Ethical ScopeA Systemic Approach to the Oversight of Machine Learning Clinical TranslationThe Need for a Global Approach to the Ethical Evaluation of Healthcare Machine LearningA Research Ethics Framework for the Clinical Translation of Healthcare Machine LearningEmerging Paradigms for Ethical Review of Research Using Artificial Intelligence Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Promoting the healing of infected diabetic wound by an anti-bacterial and nano-enzyme-containing hydrogel with inflammation-suppressing, ROS-scavenging, oxygen and nitric oxide-generating properties
Authors: Chenxi Tu, Huidan Lu, Tong Zhou, Wanying Zhang, Liwen Deng, Wangbei Cao, Zhijian Yang, Zhaolong Wang, Xinyu Wu, Jie Ding, Feng Xu, Changyou Gao
Journal: Biomaterials (2022)
Improved performance and robustness of multi-task representation learning with consistency loss between pretexts for intracranial hemorrhage identification in head CT
Authors: Sunggu Kyung, Keewon Shin, Hyunsu Jeong, Ki Duk Kim, Jooyoung Park, Kyungjin Cho, Jeong Hyun Lee, GilSun Hong, Namkug Kim
Journal: Medical Image Analysis (2022)
Leukotriene receptor antagonists and risk of neuropsychiatric events in children, adolescents and young adults: a self-controlled case series
Authors: Ji Soo Park, Yoo Jung Cho, Je-Yeon Yun, Hye Jin Lee, Jinho Yu, Hyeon-Jong Yang, Dong In Suh
Journal: European Respiratory Journal (2022)

Background Leukotriene receptor antagonists (LTRAs) are widely used for asthma and allergic rhinitis (AR), but concerns about the risk of neuropsychiatric events (NPEs) have been raised since the first Drug Safety Communication by the US Food and Drug Administration in 2008. This study evaluates the association between LTRA use and NPEs in children, adolescents and young adults with asthma or AR. Methods A self-controlled case series study was conducted using the Korean National Health Insurance Service claims database from two 3-year observation periods (observation period 1 (Obs1): 2005–2007; observation period 2 (Obs2): 2016–2018). Asthma or AR patients aged 3–30 years who were prescribed LTRAs and diagnosed with NPEs were included. The incidence rate ratios (IRRs) for the exposed period and risk periods (1–3, 4–7, 8–14, 15–30, 31–90 and &gt;90 days from initiation of LTRA) compared with unexposed periods were calculated using conditional Poisson regression. Subgroup analysis according to age group, type of NPEs and indication of LTRA was performed. Results Among 17 001 included patients, the risk of NPEs increased in Obs2 (IRR 1.11, 95% CI 1.00–1.22), but did not increase in Obs1. Risk was increased during risk periods 4–7 days (IRR 2.36, 95% CI 1.99–2.76) and 8–14 days (IRR 1.78, 95% CI 1.46–2.15) after initiation of LTRA, particularly in adolescents (IRR 1.28, 95% CI 1.05–1.55) and young adults (IRR 1.14, 95% CI 1.02–1.28), while risk was decreased in children (3–11 years). Risk was not increased for any single type of NPE. AR patients were at increased risk (IRR 1.19, 95% CI 1.01–1.39), but not those with asthma. Conclusions Overall, risk of NPEs with LTRA use differed between risk periods and subgroups. Physicians should prescribe LTRAs according to indications and inform patients about possible NPEs.
Correspondence on “Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis” by Maggi <i>et al</i>
Authors: Jean Roudier
Journal: Annals of the Rheumatic Diseases (2022)

Correspondence on "Isolation of HLA-DRnaturally presented peptides identifies T-cell epitopes for rheumatoid arthritis" by Maggi et alThe article titled 'Isolation of HLA-DR naturally presented peptides identifies T cell epitopes for rheumatoid arthritis' reports the elution and characterisation by mass spectrometry of 'naturally processed' peptides from the synovial fluid and synovium of patients with rheumatoid arthritis. 1 It uses state of the art technology to produce monocyte-derived dendritic cells and analyse the peptides associated with their Human Leucocyte Antigen DR molecules by mass spectrometry.However, the whole project is based on the a priori hypothesis that RA develops in the synovium and that only synovium-derived antigens are relevant.Thus, dendritic cells are pulsed with IgG-depleted, albumin-depleted synovial fluid or synovial tissue (This eliminates any antigen contained in an immune complex.).Later, among the analysed proteins/peptides, sequences from skin-specific proteins are discarded (this would eliminate filaggrin) and citrullinated proteins are specifically selected.This way of constructing a study makes sure that nothing new will be found: RA 'relevant' autoantigens will be found in synovial extracts, some of them citrullinated…so what?Besides this conception bias, the study ignores a peculiarity of HLA-DR processing in the context of RA.Indeed, the severe RA-associated HLA-DRB1*0401 allele has super efficient processing properties due to original intracellular route 2 and the results should consider whether the DC donor expresses HLA-DRB1*0401 or not.Finally, data critical to understand the article are presented in table 1, under a highly confusing format: column 2, titled 'HLA-DRB1 alleles', presents HLA-DRB1 genotypes but fails to explain whether they belong to dendritic cells or to synovium.It is my understanding that they actually indicate the DC donor's genotypes in the upper 14 lines and the synovium donor's genotypes in the lower three lines, but if this is correct, then it is highly confusing.Where RA starts, which antigen(s), citrullinated or not, trigger(s) the initial event(s) by activating (helper?) T cells is unknown and this high tech, high bias study will not help clarifying these issues.
When part time means full time: the GP paradox
Authors: Simon Hodes, Shan Hussain, Ayan Panja, Ellen Welch, Rosie Shire
Journal: BMJ (2022)

Recent workforce data from NHS digital once again show a decline in GP numbers.The statistics are concerning.Despite government promises for 6000 more GPs by 2024, the total number of fully-qualified full-time equivalent (FTE) GPs in England dropped from 29 320 to 27 848 over the five-year period from December 2016 to December 2021.The 1,472 FTE GPs lost to the profession during this five year period represent a 5% reduction in the GP workforce.At the same time, the number of patients registered with GPs increased by about 3.3m.
Retraction Notice to: circTulp4 functions in Alzheimer’s disease pathogenesis by regulating its parental gene, Tulp4
Authors: Nana Ma, Jie Pan, Yi Wen, Qi Wu, Bo Yu, Xi Chen, Jun Wan, Wei Zhang
Journal: Molecular Therapy (2022)

(Molecular Therapy 29, 2167–2181; June 2021) This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Concern has been raised by a reader that research reported in the article duplicates figures and reuses data from prior publications without attribution. After investigation of the concerns raised, the editors found the following reuse of data without attribution: Figure 1B in this article is identical to Ma et al., 2020, FASEB J. 34, 10342–10356, https://doi.org/10.1096/fj.201903157R, Figure 2B. Figure 1D in this article is identical to Ma et al., 2019, Mol. Ther. Nucleic Acids 18, 1049–1062, https://doi.org/10.1016/j.omtn.2019.10.030, Figure 2A. Figure 1F in this article is identical to Ma et al., 2019, Mol. Ther. Nucleic Acids 18, 1049–1062, https://doi.org/10.1016/j.omtn.2019.10.030, Figure 2B. Figure 1A in this article reuses data from Ma et al., 2020, FASEB J. 34, 10342–10356, https://doi.org/10.1096/fj.201903157R, Figure 2E. Figure S1 in this article is identical to Ma et al., 2019, Mol. Ther. Nucleic Acids 18, 1049–1062, https://doi.org/10.1016/j.omtn.2019.10.030, Figure 3. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The corresponding authors have agreed to the retraction. RETRACTED: circTulp4 functions in Alzheimer’s disease pathogenesis by regulating its parental gene, Tulp4Ma et al.Molecular TherapyFebruary 9, 2021In BriefThis article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). This article has been retracted at the request of the Editor-in-Chief. Concern has been raised by a reader that research reported in the article duplicates figures and reuses data from prior publications without attribution. After investigation of the concerns raised, the editors found the following reuse of data without attribution: Figure 1B in this article is identical to Ma et al., 2020, FASEB J. Full-Text PDF Open Archive
Left atrial disease and left atrial reverse remodelling across different stages of heart failure development and progression: a new target for prevention and treatment
Authors: Riccardo M. Inciardi, Andrea Bonelli, Tor Biering‐Sorensen, Matteo Cameli, Matteo Pagnesi, Carlo Mario Lombardi, Scott D. Solomon, Marco Metra
Journal: European Journal of Heart Failure (2022)

The left atrium is a dynamic chamber with peculiar characteristics. Stressors and disease mechanisms may deeply modify its structure and function, leading to left atrial remodelling and disease. Left atrial disease is a predictor of poor outcomes. It may be a consequence of left ventricular systolic and diastolic dysfunction and neurohormonal and inflammatory activation and/or actively contribute to the progression and clinical course of heart failure through multiple mechanisms such as left ventricular filling and development of atrial fibrillation and subsequent embolic events. There is growing evidence that therapy may improve left atrial function and reverse left atrial remodelling. Whether this translates into changes in patient's prognosis is still unknown. In this review we report current data about changes in left atrial size and function across different stages of development and progression of heart failure. At each stage, drug therapies, lifestyle interventions and procedures have been associated with improvement in left atrial structure and function, namely a reduction in left atrial volume and/or an improvement in left atrial strain function, a process that can be defined as left atrial reverse remodelling and, in some cases, this has been associated with improvement in clinical outcomes. Further evidence is still needed mainly with respect of the possible role of left atrial reverse remodelling as an independent mechanism affecting the patient's clinical course and as regards better standardization of clinically meaningful changes in left atrial measurements. Summarizing current evidence, this review may be the basis for further studies.
Estimated incidence, prevalence, mortality, and registration of childhood cancer (ages 0–14 years) in the WHO Eastern Mediterranean region: an analysis of GLOBOCAN 2020 data
Authors: Ibtihal Fadhil, Ranin Soliman, Sawsan Jaffar, Sawsan Al Madhi, Raya Saab, Asim Belgaumi, Alaa Elhaddad
Journal: The Lancet Child & Adolescent Health (2022)
Methods for the assessment of human airway ciliary function
Authors: Claire L. Jackson, Mathieu Bottier
Journal: European Respiratory Journal (2022)

<b>Airway ciliary function analysis underpins PCD diagnostics and <i>ex vivo</i>/<i>in vitro</i> mucociliary clearance studies. It is an important measure of airway culture model integrity in health and after microbial/viral infections or airway drug therapies.</b>https://bit.ly/3EXsG5J